Indazole preservatives for aqueous synthetic resin containing compositions

ABSTRACT

AQUEOUS COMPOSITIONS THAT ARE SUBJECT TO DECOMPOSITION AND SPOILAGE BY THE ACTION OF BACTERIA ARE PRESSERVED BY INCORPORATING IN THEM A SMALL AMOUNT OF A BIOCIDAL INDAZOLE.

INDAZOLE PRESERVATIVES FOR AQUEOUS SYN- THETIC RESIN CONTAINING'COMPOSITIONS Pasquale P. Minieri, Woodside, N.Y., assignor to Tenneco Chemicals, Inc.

No Drawing. Continuation-impart of abandoned application Ser. No. 201,194, Nov. 22, 1971. This application Apr. 24, 1972, Ser. No. 247,084 The portion of the term of the patent subsequent to Dec. 18, 1990, has been disclaimer] Int. Cl. C08d 11/00; C08f 45/64; C09d /14 US. Cl. 260-29.6 MN 18 Claims ABSTRACT OF THE DISCLOSURE Aqueous compositions that are subject to decomposition and spoilage by the action of bacteria are preserved by incorporating in them a small amount of a biocidal indazole.

This is a continuation-in-part of my copending application Ser. No. 201,194, whichwas filed on Nov. 22, 1971 and which has been abandoned.

This invention relates to a process for the preservation of aqueous compositions that are emulsions, dispersions, or solutions of organic substances that are subject to microbial attack.

Aqueous compositions of organic substances, such as latex paints, emulsified cutting oils, adhesives, hydraulic fluids, pulp dispersions used in paper making, and cosmetic soaps, creams, and lotions, in the absence of an effective preservative are subject to attack b putrefactive bacteria which results in a reduction in viscosity, development of color, development of foul odors, formation of slime, breaking of emulsions, and the possibility of skin infections in people handling these materials.

A number of materials have been proposed as preservatives for the organic substances in aqueous compositions, but none meets all of the requirements that have been established for such preservatives. For example, formaldehyde and formaldehyde-release compounds are relatively volatile and do not give long-term protection. Organic mercury compounds are very effective as preservatives, but their use is limited because of their high mammalian toxicity. In order to be useful as the preservative in aqueous compositions which are subject to spoilage resulting from the action of microorganisms, the compound must meet the followingrequirements: It should be effective against the microorganisms rapidly and at very low concentrations; it should be stable and soluble to some degree in water; it should be non-toxic and non-irritating to the skin in the amounts employed; it should be miscible with the organic solvents and other compounds that are commonly employed in the compositions subject to spoilage; it should be effective over a wide range of pH values so that it can be used in formulations of varied composition and pH; it should be free from objectionable odor; and it should be relatively low in cost.

In accordance with,this invention, it has been found that indazole and a wide variety of substituted indazoles satisfy the foregoing requirements and are effective as preservatives for aqueous surface-coating compositions and other aqueous compositions that are subject to microbial attack. Among the indazoles that have been found to be effective as preservatives for aqueous compositions are those having the structural formula 3,814,7l4 Patented June 4, 1974 wherein X represents halogen, nitro, acoyl, acoylamino, aroylamino, alkyleneimino having 1 to 8 carbon atoms, (halobenzylidene)amino, (alkylbenzylidene)amino, (hydroxybenzylidene)amino, (nitrobenzylidene)amino, lower alkyl, lower alkoxy, trihalomethyl, carboalkoxy, 402R, Or

Y represents hydrogen, halogen, acoylamino, alkyleneimino having 1 to 8 carbon atoms, cyano, hydroxyl, carboalkoxy, or phenyl;

R represents lower alkyl, lower haloalkyl, phenyl, halophenyl, hydroxyphenyl, alkylphenyl, nitrophenyl, alkylamino, or amino;

n represents a number in the range of zero to four; and

Z represents hydrogen or a group as hereinafter defined.

A preferred group of indazoles for use as preservatives for aqueous compositions includes those in which Z represents a group that hydrolyzes to some extent when the substituted indazole is incorporated into an aqueous composition to a hydrolysis product that comprises an indazole in which the Z substituent represents hydrogen. Particularly satisfactory results are obtained when the products of hydrolysis include at least one additional compound that has bactericidal activity, such as formaldehyde, acetaldehyde, acrolein, hexamethylenetetramine, or ethylene glycol. Among the many effective hydrolyzable compounds are those in which Z represents the group wherein E represents oxygen or sulfur; Z represents hydroxyl, thiol, halogen, thiocyanato, thioalkyl, alkoxy, or acyloxy; and n represents a number in the range of O to 4. The preferred compounds in this group are those in which E represents oxygen, Z represents hydroxyl, halogen, or thiocyanato; and n represents a number in the range of 0 to 2. The following are examples of these compounds:

N -hydroxymethyl-3-chloroindazole, N -hydroxymethyl-5,7-dichloroindazole, N -hydroxymethyl-6-acetaminoindazole, N -chloromethyl-3-chloro-6-nitroindazole, N -chloromethyl-5,6-dichloroindazole, N -bromomethyl-3-bromo-6-nitroindazole, N -iodomethyl-S-propionylaminoindazole, N -thiocyanatomethyl-3-chloro-5-nitroindazole, N -methoxymethyl-5,7-dibromoindazole, N -acetoxymethyl-3,5,7-trichloroindazole, N -mercaptomethyl-5,6-dichloroindazole, N -acetoxymethoxymethyl-S-chloroindazole, and N -propionoxymeththiomethyl-3,5,7-trichloroindazole.

In another group of hydrolyzable substituted indazoles, Z represents the group wherein R represents hydrogen, lower alkyl, lower nitroalkyl, lower haloalkyl, phenyl, nitrophenyl, hydroxyphenyl, halophenyl, alkylphenyl, alkenyl having 2 to 4 carbon atoms, alkynyl having 2 to 4 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms; R" represents hydrogen or lower alkyl; a represents 1 or 2; 0 represents 0 or 1; and 2' has the aforementioned significance. The preferred compounds in this group are those in which R is hydrogen, methyl, or ethyl; R is hydrogen; Z is hydroxyl, halogen, or thiocyanato; a is 1; and c is 0 or 1. Examples of these compounds include the following:

N -(Z-hydroxyethyl)-3-chloroindazole, N -(2-hydroxyethy1) -3-chloro-5-nitroindazole, N -(Z-hydroxyethyl)-5,7-dichloroindazole, N (2-chloroethyl)-5,6-dinitroindazole,

N (N-n-butylcarbamyl) -5,6-dinitroindazole,

N [N- 3,4-dichlorophenyl) carbamyl] -6-nitroindazole,

N [N- 3,4-dichlorophenyl carbamy1]-6- 3,4-dichlo robenzylidene) aminoindazole,

N -thiolacetyl-5,7-dichloroindazole,

N -glycoly1-3-ehloro-6-acetaminoindazole,

N (p-hydroxybenzoyl) -3,5-dichloroindazole,

and the like.

The indazoles in which Z represents hydrogen constitute another preferred group of preservatives for aqueous compositions. Examples of these compounds are the following:

indazole,

3-chloroindazole,

5-chloroindazole,

6-chloroindazole,

7-chloroindazole,

3,5-dichloroindazolc,

3,5,6-trichloroindazole,

5,7-dichloroindazole,

S-nitroindazole,

3-chloro-5-nitroindazole, 3-bromo-5-nitroindazole,

3 -hydroxyindazole,

3-cyanoindazole,

3-phenylindazole,

6-nitroindazole,

3-ehloro--nitroindazole, 4,5,7-trichloroindazole, 3-methyleneimino-7-chloroindazole,

6-( 3,4-dichlorobenzylideneamino)indazole, 6-(4-acetaminobenzylidenearnino)indazole, 6-(4-hydroxybenzylideneamino )indazole,

6-( 3-nitrobenzylideneamino)indazole, 6-(3-nitro-4-ch1orobenzylideneamino)indazole, 5- 3,4-dichlorobenzylideneamino indazole, 5-(3-nitro-4-chlorobenzylideneamino)indazole, 5-(2,S-dimethoxybenzylideneamino)indazole, 5-(4-acetaminobenzylideneamino)indazole,

6- 2,5 -dimethoxybenzylideneamino indazole, and 6- 3,5 -dichlorosalicylideneamino) indazole.

The substituted indazoles that are used in the practice of this invention may be prepared by any suitable and convenient procedure. For example, the N -hydroxymethyl compounds may be prepared by heating the appropriate substituted indazoles with formaldehyde or a formalde hyde-yielding material, and the N -chloromethyl compounds rnay be prepared by heating the appropriate N hydroxymethyl compounds with thionyl chloride. These reactions are generally carried out in a solvent, such as benzene, toluene, xylene, acetone, pyridine, or ethylene chloride, at the reflux temperature of the reaction mixture. The preparation and properties of many of these compounds are described in my Pats. US. 3,637,736 and US. 3,641,050.

In a preferred embodiment of this invention, the substituted indazoles are used as the preservative in a wide variety of aqueous surface-coating compositions The aqueous coating compositions that contain these substituted indazoles are stable and do not show signs of degradation caused by bacterial activity after storage at room temperature for 6 months or more. Because they provide long-lasting protection against bacterial activity without adversely affecting the pH, viscosity, drying characteristics, color, odor, and other properties of the surface-coating compositions, the preferred indazoles for use in surface-coating compositions are those that have the structural formula wherein X represents chlorine or acetamino; Y represents hydrogen or chlorine; Z" represents hydroxyl or chlorine; and n represents a number in the range of 0 to 4. Examples of these most effective bactericides in-= elude N -hydroxymethyl-3-chloroindazole, N -hydroxymethyl-S-chloroindazole, N -hydroxymethy1-5,7-dichloroindazole, N -hydroxymethyl-3,5,7-trichloroindazole, N -hydroxymethyl-4,5,6,7-tetrachlorindazole, N -l1ydroxymethyl-3,4,5,6-7-pentachloroindazole, N -hydroxymethyl-6-acetaminoindazole, N -chloromethyl-7-chloroindazole, N -chloromethyl-3-chloro-6-acetaminoindazole, and -N -chloromethyl-5,7-dichloroindazole.

The surface-coating compositions to which the substituted indazoles may be added as preservatives are aqueous dispersions that contain about 10 percent to 60 percent by weight of a water-insoluble resinous binder that is a synthetic linear addition polymer and/or an oleoresinous binder. The useful aqueous dispersions of syn thetic linear addition polymers are ordinarily prepared by the emulsion polymerization of ethylenically-un saturated monomers. Illustrative of these polymers are polyvinyl acetate; polyvinyl butyrate; polyvinyl chloride; copolymers of vinyl acetate with vinyl chloride or acrylonitrile; copolymers of vinyl chloride with acrylonitrile or vinylidene chloride; polyethylene; polyisobutylene; copolymers of styrene with butadiene, acrylonitrile, or maleic anhydride; copolymers of acrylic acid esters or methacrylic acid esters of alcohols having 1 to 8 carbon atoms with vinyl acetate, vinyl chloride, acrylonitrile, or styrene; copolymers of the aforementioned acrylic acid esters, the aforementioned methacrylic acid esters, and acrylic acid; and mixtures thereof. Suitable oleoresinous binders include drying oils, bodied drying oils, oleoresinous varnishes, alkyd resins, and mixtures thereof.

Only a small amount of the bactericidal indazole is re quired to protect the aqueous surface-coating composition from attack by bacteria. As little as 0.10 percent of one or more of these compounds, based on the weight of the composition, will bring about an appreciable im provement in the resistance of the composition to attack by bacteria. One percent or more of the bactericidal compounds can be used, but these larger amounts ordinarily do not provide further improvement in the properties of the compositions and for this reason are not usually used. While the amount of the substituted indazoles that will provide optimum protection for an aqueous surface-coat ing composition depends upon such factors as the choice of indazole, the choice of resinous binder and other ingredients of the composition and the amount of each of these materials that is used, it is generally preferred to use 0.2 percent to 0.4 percent of the bactericidal indazole, based on the weight of the surface-coating composition.

In addition to the resinous binder and the bactericidal compound, the surface-coating compositions may contain various auxiliary materials, such as pigments, extenders, solvents, dyes, defoaming agents, driers, thickeners, emulsifiers, plasticizers, and the like in the amounts ordinarily used for these purposes.

The bactericidal indazoles may be incorporated into the surface-coating compositions by any convenient procedure. For example they can be combined with the pigments and other ingredients to form a pigment phase that is mixed with the resinous binder and water to form the surface-coating composition. Alternatively, they can be added to a composition that contains the resinous binder, pigment, and water. The indazoles can be added as such to the other ingredients, or they can be added as a solution in, for example, an alcohol, ether, hydrocarbon, or ketone.

The invention is further illustrated by the following examples.

Percent total decrease in viscosity Viability incubation period (days) Incubation period (days) B. The paints prepared in Example 1A were evaluated by the following procedures:

A mixed bacterial inoculum consisting of Pscurlomonas aeruginosa ATCC 10145, Aerobacter aerogenes ATCC 7256, Bacillus subtilis, Bacillus megslerium and Bacillus lichenz'formis was prepared by incubation of inoculated (0.5 ml.) milk dilution bottles containing 50 ml. solidified Trypticase-Soy Agar.

After incubation for 18 to 24 hours at 35 C., the cultures were removed from the agar surface, diluted to an appropriate volume in phosphate buffer (0.05 M, pH 7.0),

that the final level of bacteria was between 0.5 and 30 3 1O per gram of paint. After thorough mixing, the 690 paints were incubated at 35 C. under 90 percent relative 345 humidity. At ntervals durmg the incubation, measure 150 ments of Vlablllty of the bacteria and viscosity of the paint were made. The viability test was carried out by 20 adding an aliquot of the paint to Trypticase-Soy Broth, incubating for 48 hours at C., and then streaking it on a Trypticase-Soy Agar plate. After a 24 hour incubation period at 35 C., the plates were examined for growth along the streak. The results obtained are reported in The viscosity of the paint samples was measured with a Brookfield Viscometer using a No. 3 spindle at rpm. The percentage decrease of the viscosity of each of the treated paints during the incubation period is reported in Table I.

TABLE I.SUBSTI'IUTED INDAZOLES AS PRESERVATIVES FOR POLYVINYL ACETATE LATEX PAINT tlon of biocide (percent) 1 and inoculated into 300 gram portions of the test paints. The amount of the culture added to the paint was such Small amounts of the bactericidal indazoles of this invention or comparative biocides were added to portions of this paint, and the resulting treated paints were mixed 30 for 24 hours on a ball-mill.

Concentra- 7 EXAMPL 1 A. A. polyvinyl acetate latex paint was prepared by mixing together the following materials:

Parts by weight Water 481.5 25% aqueous solution of sodium salt of maleic anhydride/diisobutylene copolymer Potassium pyrophosphate Long chain fatty acid alkanolamide Defoamer Ethylene glycol u 1%% aqueous solution of Hydroxyethylcellulose Aqueous emulsion containing 55% of polyvinyl acetate 1299 Diethyl ether of diethylene glycol Titanium dioxide Calcium metasilicate s This paint had the following properties as determined by standard paint testing procedures:

Brookfield viscosity (No. 4 spindle,

60 rpm.) cps 800 pH 7-8 25 Table I as (growth present) or (growth absent).

Bioclde Viscosity K.U

Yellowness index Example number 1 G wsuuws N hydroxymcLhyl-5,6-dinitroindazole. .s

(Ina 11 39 24 v 5 P 3 2 B2 1L N -ehloromethyl3-chlor0-6-nitroindazole.

an an ma co 2 R M Son 3 1Q m. Mew".-. N -(5,G diilitroiudazolyl-N -mcthyl) piporidino 1S "WWW..." N-(tinitroindazolyl-N methyl)hoxamcthylcnoiminc..mm;

TABLE I--Contlnued Concentratlon of biocide (percent) 1 Biocide yl-M-methyD-hexamethyleneinune.

Example number 1U =-t.... N-(ti-chloro-G-nitroindazolyl-N -methyl)-hexamethylene tetraammonium chloride.

Comp. Ex. A.-. Formaldehyde (37% stabilized).......

Comp. Ex. B-.. Phenylmereuric acetate (18% Hg)...

EXAMPLE 3 A cosmetic lotion was prepared from the following materials:

Parts by weight 7.5

g ingredi- C. The aqueous phase aqueous phase slowly with stirring until the preparation had cooled perature, the

EXAMPLE 4 An aqueous cutting oil emulsion was prepared by the following procedure: A mixture of a light mineral oil, an pling agent, minor amounts of other components was diluted with rty parts of water per part of said mixture to form an mulsion. To a sample of this emulsion was added 0.3

yrnethyl-5,7-dichloroindae and 5 percent by weight of a cutting oil emulsion al growth after Percent total decrease in viscosity Incubation period (days) Viability incubation period (days) yeti'yiflQfiiidfiih?HEHVZIHVFYXHQQ 6-1425) Sorbitan sesquioleate All of the ingredients except the preservative and water were heated together to 75 C., and the remainin cuts were heated together to 77 was added to the non- 1642 35 which was continued This Paint bad the following P perties: After standing for 2 weeks at room tern lotion showed no sign of bacterial growth.

tion of biocide (percent) 1 Mineral oil 37.5 Beeswax 2 Polyox 12 Water 46.2 N -hydroxymethyl-3,S-dichloroindazole to room temperature.

organic emulsifier, an aliphatic alcohol con and to D e EXAMPLE 2 A. An acrylic latex paint was prepared by mixing to- Parts by weight 1 8 *Petrolatum anhydride/diisobutylene copolymer copolymer (66% ethyl acryl'ate, 32.5% methyl acrylate, and 1.5% acrylic acid) r.p.m.) cps 1250 40 Small amounts of the biocidal compounds of this inportions g treated paints were mixed B. The paints prepared by the foregoing procedure P r y Weight of N1-hydT0X zo which was badly contaminated with bacteri TABLE II.SUBSTIIUIED INDAZOLES as PRESERVATIVES FOR ACRYLIC LATEX PAINT Concentra- Biocide gether the following materials:

Water Alkyl aryl ether surfactant 25% aqueous solution of sodium salt of maleic Defoamcr 2% aqueous solution of hydroxyethylcellulose Ethylene glycol Titanium dioxide Mica (waterground) Calcium carbonate Ammonium hydroxide (28% Aqueous dispersion containing 46% acrylic ester Viscosity K.U Brokfield viscosity (No. 3 spindle,

Yellowness index vention or comparative biocides were added to of this paint, and the resultin for 24 hours on a ball-mill.

were evaluated by the test procedures described in Example 1B. The results obtained are given in Table II.

Example number 2C..l..- u. n N hydroxymethyl-3,5-dichloroindazole...

2E N -hydroxymethyl-6-acetaminoindazoie Comp. Ex, E." Phenyimercuric acetate (18% Hg).

industrial use. The inoculated sample was shaken at room temperature. After 24 hours and 48 hours swabs of the sample were streaked on nutrient agar plates which were incubated for 48 hours at 30 C. before examination. In neither case was there bacterial growth on the agar plates.

Each of the other indazoles disclosed herein can be used in a similar manner to prevent the growth of bacteria in aqueous compositions that contain organic materials that are subject to deterioration by the action of bacteria.

The terms and expressions which have been employed are used as terms of description and not of limitation. There is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed.

I claim:

1. An aqueous surface-coating composition that is resistant to spoilage by the action of bacteria that consists essentially of (a) a water-insoluble resinous binder prepared by the emulsion polymerization of ethylenicallyunsaturaed monomers selected from the group consisting of vinyl acetate, vinyl butyrate, vinyl chloride, acrylonitrile, vinylidene chloride, ethylene, isobutylene, styrene, butadiene, acrylic acid esters or methacrylic acid esters of alcohols having 1 to 8 carbon atoms, and mixtures thereof and (b) 0.1 percent to 1.0 percent, based on the weight of said composition, of a bactericidal compound having the structural formula H zll wherein X represents chlorine or acetamino; Y represents hydrogen or chlorine; Z" represents hydroxyl or chlorine; and n represents a number in the range of to 4.

2. An aqueous surface-coating composition as set forth in claim 1 wherein Z represents hydroxyl.

3. An aqueous surface-coating composition as set forth in claim 1 wherein X represents chlorine:

4. An aqueous surface-coating composition as set forth in claim 1 wherein the bactericidal compound is N -hydroxymethyl-S-chloroindazole.

5. An aqueous surface-coating comopsition as set forth in claim 1 wherein the bactericidal compound is N -hydroxymethyl-3,5-dichloroindazole.

6. An aqueous surface-coating composition as set forth in claim 1. wherein the bactericidal compound is N -hydroxymethyl-S,7-dichloroindazole.

7. An aqueous surface-coating composition as set forth in claim 1 wherein the bactericidal compound is N -hydroxymethyl-4,5,7-trichloroindazole.

8. An aqueous surface-coating composition as set forth in claim 1 that contains about 10 percent to 60 percent by weight of said water-insoluble resinous binder.

9. An aqueous surface-coating composition as set forth in claim 1 that contains 0.2 percent to 0.4 percent by weight of said bactericidal compound.

10. A surface-coating composition that is resistant to the action of bacteria that comprises an aqueous composition consisting essentially of about 10 percent to 60 percent by weight of polyvinyl acetate and 0.1 percent to 1.0

12 percent by weight of N -hydroxymethyl-5,7-dichloro indazole.

11. The process for preventing bacteria-caused spoilage in an aqueous surface-coating composition that is normally subject to such spoilage, said aqueous composition consisting essentially of a water-insoluble resinous binder prepared by the emulsion polymerization of ethylenicallyunsaturated monomers selected from the group consisting of vinyl acetate, vinyl butyrate, vinyl chloride, acrylonitrile, vinylidene chloride, ethylene, isobutylene, styrene, butadiene, acrylic acid esters or methacrylic esters of alcohols having 1 to 8 carbon atoms, and mixtures thereof, that comprises incorporating in said composition 0.1 percent to 1.0 percent, based on the weight of the composition, of a bactericidal compound having the structural formula wherein X represents chlorine or acetamino, Y represents hydrogen or chlorine, Z" represents hydroxyl or chlorine, and n represents a number in the range of 0 to 4.

12. The process of claim 11 wherein Z" represents hydroxyl.

13. The process of claim 11 wherein X represents chlorine.

14. The process of claim 11 wherein the bactericidal compound is N -hydroxymethyl-S-chloroindazole.

15. The process of claim 11 wherein the bactericidal compound is N -hydroxymethyl-3,5-dichloroindazole.

16. The process for preventing bacteria-caused spoilage in an aqueous surface-coating composition that is normally subject to such spoilage, said aqueous composition consisting essentially of a water-insoluble resinous binder prepared by the emulsion polymerization of ethylenicallyunsaturated monomers selected from the group consisting of vinyl acetate, vinyl butyrate, vinyl chloride, acrylonitrile, vinylidene chloride, ethylene, isobutylene, styrene, butadiene, acrylic acid esters or methacrylic acid esters of alcohols having 1 to 8 carbon atoms, and mixtures thereof, that comprises incorporating in said composition 0.1 percent to 1.0 percent, based on the weight of the composition, of N -hydroxymethyl-5,7-dichloroindazole.

17. The process of claim 11 wherein the bactericidal compound is N -hydroxymethyl-4,5,7-trichloroindazole.

18. The process of claim 11 wherein the bactericidal compound is N -hydroxymethyl-6-acetaminoindazole.

References Cited UNITED STATES PATENTS 3,317,448 5/1967 Prindle et al. 26029.6 MN 3,325,436 6/1967 Prindle et al. 260-29.6 MN

LUCILLE M. PHYNES, Primary Examiner Us. 01. X.R.

lO6-15 R; 260-17 R, 29.6 HN & N, 29.7 N, 41 A & B, 78.5 R & T, 83.7, 85.5 ES & XA, 86.1 E, 89.1, 92.8 A, 94.8, 94.9 A & GB; 424-78, 81, 244, 273, 365 

